WO2009/105500 describes ERK inhibitors, including procedures for making them and procedures for preparing pharmaceutical compositions comprising the ERK inhibitors. Described pharmaceutical compositions include solid form preparations including powders, tablets, dispersible granules, capsules, cachets and suppositories for direct administration to a patient; liquid form preparations including solutions, suspensions and emulsions for direct administration to a patient; aerosol preparations suitable for inhalation; solid form preparations which are intended to be converted, shortly before use, to liquid form preparations, including solutions, suspensions and emulsions for subsequent administration to a patient; and transdermal compositions including creams, lotions, aerosols and/or emulsions for direct application to the patient or administration via transdermal patch.
(S)—N-(3-(6-isopropoxypyridin-3-yl)-1H-indazol-5-yl)-1-(2-(4-(4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-3-(methylthio)pyrrolidine-3-carboxamide, a specific ERK inhibitor described in WO2009/105500, is most stable in crystalline hydrate Form 2. This form has poor solubility, and in order to efficiently prepare certain pharmaceutical compositions for administration to patients including tablet and capsules suitable for safe and effective oral administration, it is highly desirable to create amorphous dispersions to improve solubility wherein the amorphous form of the drug shall have higher apparent solubility compared to its crystalline counterparts.
The present invention provides a dispersion of (S)—N-(3-(6-isopropoxypyridin-3-yl)-1H-indazol-5-yl)-1-(2-(4-(4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-3-(methylthio)pyrrolidine-3-carboxamide having improved solubility which allows for efficient preparation of tablets and capsules suitable for safe and effective oral administration to a patient.